Will Current Clinical Trials Answer the Most Important Questions About Prostate Adenocarcinoma?

Will Current Clinical Trials Answer the Most Important Questions About Prostate Adenocarcinoma?

Thompson and Seay have attempted to provide a concise overview of the
treatment of both
localized and metastatic prostate cancer. Also, they have listed most of
the current clinical trials focusing on these issues, along with two current
trials addressing the prevention of the disease. There is certainly no
getting away from the fact that, even with the plethora of publications
dealing with prostate cancer (1,643 in 1994 alone, as the authors point
out), there are major gaps in our fund of knowledge about this disease
entity.

Prostate Cancer Prevention Trial

The Prostate Cancer Prevention Trial, of which Thompson is the principal
investigator, should be a landmark study. As with any study, especially
successful ones, there will be abundant detractors. Already there is a
background chorus questioning whether Finasteride (Proscar) is the right
agent to be used in a prevention trial of this magnitude. The fact of the
matter is that, at present, there is a dearth of compounds available for
a trial of this sort, and Thompson and colleagues are to be commended for
pressing ahead with this timely initiative of prevention. It should be
pointed out that the accrual rate of this trial has been met, and all efforts
are now focused on follow up.

One word of caution about this study is in order. All study participants
are to have a prostate biopsy at 7 years following randomization, and the
sample size has been determined to account for those who are not fully
evaluable. Nevertheless, the fact that all subjects are biopsied may not,
in itself, be foolproof. We all have cohorts of patients who have undergone
many biopsies before the diagnosis of prostate cancer is made. These are
patients in whom prostate cancer is strongly suspected, eg, those with
a rising prostate-specific antigen (PSA) level, in whom numerous biopsies
are all negative. Nevertheless, to have patients agree to a biopsy at the
end of the trial is a coup
for the planners of the study.

Prostate Cancer Intervention Versus Observation Trial

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) poses
some interesting problems. Although accrual is increasing, practically
all of the patients come from Veterans Administration (VA) hospitals. The
point to be made is that, at present, a study of radical prostatectomy
vs "observation" is probably impossible to carry out, except
in the setting of socialized medicine that exists in VA hospitals. It must
be remembered that radical prostatectomies represent a substantial portion
of the surgery performed by many urologists in both private and academic
settings resulting in a substantial portion of income.

Evaluating Treatments for Localized Disease

I agree with the authors' assessment that very few studies have compared
the efficacy of different modalities of therapy for localized disease.
In particular, as they point out, it would be of utmost importance to have
brachytherapy compared with external-beam radiation therapy. This question
is currently being considered by the Radiation Therapy Oncology Group (RTOG).

It is true that there are no head-to-head comparisons of the various
treatment regimens for localized disease. I must remind the authors that
there have been two attempts to compare radical prostatectomy and external-beam
radiation. Both studies, one by the National Prostate Cancer Project and
a more recent trial by the Southwest Oncology Group, had to be closed due
to lack of accrual. I submit that, despite their clinical relevance, some
studies unfortunately cannot be carried out to completion. Investigators
must contend with economics, as well as the beliefs of urologists and radiologists
in their respective disciplines. In addition, training programs rely on
large
numbers of cases. Thus, to compare these two disparate treatment modalities
is problematic, to say the least.

I agree with Thompson and Seay that prostate cancers are frequently
indolent. However, the current dilemma is that there is no way to discern
which cancers are indolent. In my opinion, the answers about which tumors
are indolent and which are virulent will come primarily from molecular
studies.

Studies of Neoadjuvant Therapy

As far as neoadjuvant studies are concerned, trials are now being conducted
to define the role of neoadjuvant therapy prior to definitive therapy.
It is only through continuing studies and the passage of time that we will
be able to determine whether the decrease in positive margins translates
into an
increase in overall and cause-specific survival. Also, the question of
length of neoadjuvant therapy prior to definitive therapy is being investigated.
The RTOG is ready to launch a study of adjuvant radiotherapy with and without
hormonal therapy, in this instance, the antiandrogen bicalutamide (Casodex).

The authors have provided readers with a concise list of current trials,
which may prompt some readers to enroll patients into appropriate protocols.
It is necessary for all of us involved in urologic oncology to make our
patients aware of protocols that are suitable for their particular situation.
Although, as the authors point out, "... many of these answers may
not be available for several years," we must all be advocates of clinical
trials. Educating our patients that clinical trials reflect the latest
knowledge about urologic oncology is beneficial to our patients and to
our profession.

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